Does Anyone Know How to Determine the Wild-Type and Risk Allele in a SNP?

[topghetto]

Hi everyone,

I am bit unsure on how to determine a wild-type (normal) and a risk-allele of a SNP. According to this resource (http://www.hgmd.cf.ac.uk/docs/mut_nom.html) it says, for e.g., 76A>C denotes that at nucleotide 76 a A is changed to a C) - so, what I have taken from this is that 'A' is the norm and 'C' is the mutation. However, according to my GeniticGenie report, it says I am homozygous (CC allele) for AHCY-01 but, according to this website: https://www.pharmgkb.org/variant/rs819147, it has C > T - meaning that the C is the norm and T is the mutation so, that made me a bit baffled.

Shortly, I realised that the website also has a table for the frequency for both versions of the SNP: C and T, where C has a lower total frequency and T has a higher total frequency. I cannot remember where I read this but, apparently, the popular allele is considered the wild-type and the non-popular allele is considered the 'risk allele'. If this true, would this make sense as to why my GeneticGenie report says I am homozygous for the AHCY-01 SNP?

The reason why I am so fussed about this is because I want to examine my other SNPs that are not covered by GeneticGenie. So, really, what I am asking is if I want to determine my wild-type and risk alleles, do I also need to take in the frequency of the alleles into consideration?

@Valentijn I hope you do not mind me tagging you in this thread because I see that you are knowledgeable in SNPs

I do apologise if this question (or a similar one) has already been covered in another of thread.

 

[Valentijn]

I cannot remember where I read this but, apparently, the popular allele is considered the wild-type and the non-popular allele is considered the 'risk allele'.

Usually the more common allele is the wild-type. But from what I recall, it's more accurate to describe the wild-type as being the allele which humanity has had for a verrrry long time. One way that is at least sometimes determined is by comparing the same SNP to other primates. So usually the wild-type will be the more common allele, but sometimes it won't be, and frequently both alleles will have very similar prevalence rates.

The less prevalent allele is called the "Minor Allele" (MA), and its prevalence rate is the "Minor Allele Frequency" (MAF). The more prevalent allele can be called the "Major Allele". If the major allele is the one being marked as risky, it's a good sign that the research or other source of the claim of riskiness warrants closer scrutiny. And if the major allele really is riskier, it's usually more accurate to think of the minor allele as being beneficial. Especially since when that happens it's typically a very small effect size, which isn't causing anyone any problems.

If this true, would this make sense as to why my GeneticGenie report says I am homozygous for the AHCY-01 SNP?

Regarding the Yasko claims about AHCY, which are reported by GeneticGenie, the assignment of "risk alleles" is completely fabricated with so scientific support. There is no research showing that any of the Yasko AHCY SNPs ever have any impact. So it's safe to cross those off and ignore them.

 

[topghetto]

Thank you so much for clearing all of this up for me, Valentijn. This now makes sense to me

 

[merylg]

I use a couple of sites. dbSNP & OpenSnp.

dbSNP gives interesting population frequency data presented in a graph form. So for example, what is common in Sub Saharan African populations may be opposite to what is common in European populations or Asian populations.

http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=819147

OpenSNP is compiled from contributor information but gives interesting pie charts. It will be biased because it basically only contains info from people looking into their own genetics.

https://opensnp.org/snps/rs819147#snpedia

Both sites often have links to research papers.

 

[topghetto]

merylg, thank you for sharing those links; I will definitely be using those two resources for next time I look into my genetics